Cyclopropane carboxylic acid esters as insecticides

ABSTRACT

CYCLOPROPANE CARBOXYLIC ACID ESTERS OF PHENOXYBUTYNYL ALCOHOLS. THE PHENYL RING MAY INCLUDE A CHLORO OR LOWER ALKYL SUBSTITUENT. THE ESTERS ARE USEFUL AS INSECTICIDES.

United States Patent 3,814,805 CYCLOPROPANF. CARBOXYLIC ACID ESTERS ASINSECTICIDES John Mervyn Osbond, Hatfield, and James Charles Wickens,St. Albans, England, assignors to Hoffman!!- La Roche Inc., Nutley, NJ.

No Drawing. Original application Apr. 27, I971, Ser. No. 139,296, nowPatent No. 3,761,506. Divided and this application Sept. 12, 1972, Ser.No. 288,463

Claims priority, application Great Britain, June 8, 1970,

27,581/70 Int. Cl. A0ln 9/24 US. Cl. 424-306 6 Claims ABSTRACT OF THEDISCLOSURE Cyclopropane carboxylic acid esters of phenoxybutynylalcohols. The phenyl ring may include a chloro or lower alkylsubstituent. The esters are useful as insecticides.

This is a division of application Ser. No. 139,296 filed Apr. 27, 1971entitled Cyclopropane Carboxylic Acid Esters, now US. Pat. No.3,761,506.

SUMMARY OF THE INVENTION In accordance with this invention, it has beenfound that esters of the formula:

wherein X is hydrogen, lower alkyl, or chlorine are useful asinsecticides.

The compounds of formula I are prepared by reacting an acid halide ofthe formula:

wherein W is chlorine or bromine;

with an alcohol of the formula:

wherein X is as above.

The compounds of formula I are also prepared by reacting a salt havingthe formula:

ll 0 IV wherein X is as above and hal is a halogen.

"ice

The compounds of formula I are further prepared by reacting a compoundof the formula:

11 0 CH: HaC \C/ Q HIC/ COCIIzCECCI-I:Cl

ll V1 with a compound of the formula:

wherein X is as above and M is an alkali metal.

DETAILED DESCRIPTION OF THE INVENTION The term lower alkyl," as usedthroughout this ap plication, comprehends both straight-chain andbranchedchain saturated alkyl hydrocarbon groups containing from 1 to 6carbon atoms such as methyl, ethyl, butyl, and isopropyl, with methylbeing preferred.

The term halogen" or halo," as used herein, when not expressly statedotherwise, includes all four halogens, i.e., bromine, chlorine, fluorineand iodine, with chlorine being preferred.

The term alkali metal," as used herein, comprehends the alkali metals ofthe first group of the periodic chart, such as sodium, potassium andlithium, with sodium being preferred.

The term triloweralkylammonium," as used herein, means the cation of thereaction salt of a carboxylic acid and a triloweralkylamine. Bytriloweralkylamine, as just used, is meant that each of the three alkylgroups attached to the amine nitrogen is a lower alkyl," as definedabove. The term triloweralkylammonium" includes cations such astriethylammonium and tri-isopropylammonium.

As mentioned above, the esters provided by this invention are useful asinsecticides. They are active against a variety of insects (particularlyagainst Musca domestica) Furthermore, these esters have been found tohave a very low mammalian toxicity. For example, 4-phenoxy-2-butynyl-2,2,3,3-tetramethylcyclopropane carboxylic has an LD of greaterthan 1600 mg./ kg. per as in mice, and 4- (4-chlorophenoxy)-2-butynyl2,2,3,3 tetramethyl-cyclopropane carboxylate has an LD of 1600 mg./g.per as in mice. These esters have shown an activity against M uscadomestica on the order of that of pyrethrin extract and DDT, and theyhave also shown an activity against bean aphids, Colorado beetle, redspider mites and codlin moth.

The esters of the invention can be used in the form of insecticidalcompositions which contain them in association with a compatible carriermaterial. Such insecticidal compositions can be made up in liquid form(e.g. as a sprayable solution or suspension) or in solid form (e.g. asas dust or granulate), either of which includes therewith a compatiblecarrier. The term compatible carrier" is used in this specification tomean a substance which is inert towards the esters of formula I, whichcan be used to dissolve, disperse or diffuse the esters withoutimpairing their effectiveness and which does not permanently damage theenvironment to which it is applied (e.g. crops, soil, equipment, etc.).For example, liquid compositions can be extended with water and dustsand granulates can be extended with inert solid carriers. Where a solidcarrier is used in the preparation of insecticidal compositions, thecarrier may be talc, finely powdered clay, silica or any similar carrierwhich does not bring about decomposition of the esters. Where the estersof formula I are formulated into liquid compositions, such compositionscan include emulsifiers and/or acceptable organic solvents. If desired,the compositions can also contain conventional additives such as wettingagents or the like, as well as other insecticidally-activc compoundsand/or synergists.

An effective amount of an insecticidal composition can be applied to aninsect-infested area using any conventionally accepted method such asspraying, dusting, etc. Desirably, solid compositions and liquidcompositions contain from about 0.5% to 257 (preferably from about 1% to10%) by weight of an ester of formula I. The choice of concentration ofan ester of formula I and the rate of application to the insect-infestedarea will, of course, depend on several factors; for example, the typeand maturity of insects present. the type of composition applied and themode of application.

It will be appreciated that the insecticidal compositions can take theform of concentrates (e.g. wettable powders or emulsion concentrates)suitable for storage and containing. for example, from about 10% to 80%by weight of an ester of formula I. The concentrate can be diluted withthe same or a different carrier to a concentration suitable forapplication to an insect-infested area. Emulsion concentrates can beprepared, for example, by dissolving an ester of formula I in anacceptable organic solvent and adding an emulsifier which is soluble inthe organic solvent.

Any organic solvent can be used including hydrocarbons (e.g., tolueneand xylene), chlorinated hydrocarbons (e.g., perchloroethylene),ketones, esters, etc. or mixtures thereof. Preferably, the solventshould be water immiscible, and the especially preferred solvents arearomatic hydrocarbons and ketones.

Surfactants are useful as emulsifiers, and when used, they suitablyconstitute from about to 15% by weight of and emulsion concentrate.Preferably, the surfactants should be non-ionic.

In accordance with this invention, among the preferred compounds offormula I are the esters having the formula:

HIC

Among the particularly preferred compounds of formula I are included thefollowing compounds of formula Ib:

4(2-chloro-phenoxy)-2-butynyl-2,2,3,3-tetramethyl-cyclopropanecarboxylate and4-(4-ehloro-phenoxy)-2-butynyl-2,2,3,3-tetramethyl-cyclopropanecarboxylate. Among the particularly preferred compound of formula I,quite particularly preferred is 4-phenoxy-2-butynyl-2,2,-3,3-tetramethyl-cyclopropane carboxylate.

One method for preparing the compounds of formula I involves reacting anacid chloride or bromide of formula II with an alcohol of formula III.

The acid chloride and acid bromide starting materials of formula II areknown substances. They can be conveniently prepared by first reactingtetramethyl-ethylene with methyl or ethyl diazoacetic acid ester in thepresence of copper powder or anhydrous copper sulfate, using excesstetramethyl-ethylene or toluene as the solvent, and subsequentlychlorinating or brominating the resulting 2,2,3,3tetramethyl-cyclopropane carboxylic acid with thionyl chloride,phosphorus tribromide, or the like. In this reaction, anhydrous coppersulfate is the preferred reagent and toluene is the preferred solvent.The acid chlorides are the preferred starting materials of formula III.

The alcohol starting materials of formula III can be prepared, forexample, by reacting a halo-butynol of the formula:

halCH -CEC-CI-I OH VIII wherein hal is as above, preferably chlorine;with an alkali metal salt of a phenol of formula VII, hereinbefore,preferably a sodium salt. In carrying out this reaction, temperature andpressure are not critical, and the reaction can be carried out at roomtemperature (about 25 C.). Generally, it is preferred to carry out thisreaction at an elevated temperature. A temperature of between 50 C. andC. is especially preferred. The reaction can be carried out in anyconventional inert organic solvent, preferably a lower alkanol, methanoland ethanol being especially preferred lower alkanols.

The reaction of an acid halide starting material of formula II with analcohol starting material of formula. III is conveniently carried out inthe presence of an acidbinding agent. In this reaction, any conventionalacidbinding agent can be used. Among the preferred acid-binding agentsare alkali metal carbonates, such as sodium carbonate, alkali metalbicarbonates, such as sodium bicarbonate, and tertiary organic amines,such as triethylaminepyridine and the like. An especially preferredacid-binding agent is pyridine. This reaction is conveniently carriedout in the presence of an inert organic solvent. Any conventional inertorganic solvent can be used. Among the preferred solvents, are includedhydrocarbons, such as benzene, toluene or xylene, ethers such as diethylether or dioxane, and halogenated hydrocarbons, such as methylenechloride, chloroform or the like. In carrying out this reaction,temperature and pressure are not critical, and this reaction can becarried out at room temperature. Generally, it is preferred to carry outthis reaction at a temperature within the approximate range of from 0 C.to 30 C., with about 20 C. being especially preferred. The reaction isalso preferably carried out under the atmosphere of an inert gas. Anyconventional inert gas may suitably be used, with nitrogen or argonbeing particularly preferred.

Another method for preparing the compounds of for mula I involvesreacting the alkali metal salt, the silver salt or thetriloweralkylamine salt of a cyclopropane carboxylic acid of formula IVwith a halide of formula V.

The alkali metal and triloweralkylamine salts of for mula IV can beprepared, for example, by treating 2,23,3- tetramethyl-cyclopropanecarboxylic acid in an inert organic solvent with a dilute aqueous alkalimetal hydroxide solution or a triloweralkylamine. In carrying out thisreaction, any conventional inert organic solvent can be utilized whichis compatible with the amine or with the hydroxide solution, as the casemay be. Among the preferred solvents are the lower alkanols, withethanol being especially preferred. In carrying out this reaction, anyalkali metal hydroxide or triloweralkylamine can be utilized. Among thepreferred hydroxides and amines are the sodium and potassium hydroxidesand triethylamine. In

carrying out this reaction, temperature and pressure are not critical,and the reaction can be carried out at room temperature.

The silver salts of formula IV can be prepared by treating alkali metalsalt of formula IV, such as the sodium salt, in an aqueous solution withsilver nitrate. In carrying out this reaction, temperature and pressureare not critical, and the reaction can be carried out at roomtemperature.

The halide starting materials of formula V can be prepared, for example,by reacting a dihalobutyne of the formula:

hal-CH CECCH,-hal IX wherein hal is as above, preferably chlorine;

with an alkali metal salt of a phenol of formula VII. The reaction issuitably carried out .in an inert organic solvent. Any conventionalinert organic solvent can be used, with a lower alkanol being preferred,methanol and ethanol being especially preferred. In carrying out thisreaction, temperature and pressure are not critical. Generally incarrying out this reaction, an elevated temperature is preferred, with atemperature of from 50 C. to 70 C. being especially preferred.

The halide starting materials of formula V can also be prepared, forexample, by treating an alcohol starting material of formula III with ahalogenating agent. Any conventional halogenatin-g agent can be utilizedin this reaction, with thionyl chloride or phosphorus tribromide inpyridine being preferred.

The reaction of an alkali metal salt, a silver salt or atriloweralkylamine salt of 2,2,3,3 tetramethyl-cycloprw pane carboxylicacid, of formula IV, with a halide of formula V is suitably carried outin an inert organic solvent. In this reaction, any conventional inertorganic solvent can be utilized with a ketone, such as acetone or methylethyl ketone, or high-boiling ether, such as diglyme being preferred. Incarying out this reaction, temperature and pressure are not critical.Generally, it is preferred to carry out the reaction at an elevatedtemperature, the reflux temperature of the reaction mixture beingespecially preferred. It is also preferred to carry out this reactionunder the atmosphere of an inert gas. In this reaction, the selection ofthe inert gas is not critical, nitrogen or argon being particularly.preferred.

Still another method for preparing the compounds of formula I involvesreacting a compound of formula V1 with an alkali metal salt of a phenolof formula VII.

The starting materials of formula VI can be prepared, for example, byreacting an acid chloride or bromide of formula II with4-chloro2-butyn-l-ol. The reaction can be carried out under similarconditions to those described earlier in connection with the reaction ofan acid chloride or bromide starting material of formula II with analcohol starting material of formula In.

The alkali metal salts of the phenols of formula VII are known and canbe prepared by conventional methods.

The reaction of a starting material of formula VI with an alkali metalsalt of a phenol of formula VII can suitably be carried out in thepresence of an inert organic solvent. In this reaction, any conventionalinert organic solvent can be utilized, such as a hydrocarbon, ahighboiling ether or a halogenated hydrocarbon. Benzene, toluene, andxylene, are the preferred hydrocarbons, diglyme is the preferred ether,and chloroform and methylene chloride are the preferred halogenatedhydrocarbons. In carrying out this reaction, temperature and pressureare not critical. Generally, it is preferred to carry out the reactionat an elevated temperature, with the reflux temperature of the reactionmixture being especially preferred. Also, it is preferred to carry outthe reaction under the atmosphere of an inert gas. In this reaction, anyconventional inert gas may be utilized, with nitrogen or argon beingparticularly preferred.

The following examples illustrate the compounds of the invention. Alltemperatures are in degree centigrade.

Example 1 7.4 g. (0.0457 mol) of 4-phenoxy-2-butyn-l-ol was dissolved in65 ml. of dry benzene and 7.5 ml. of dry pyridine was added to thesolution obtained. To this solution, there was added dropwise withstirring under a nitrogen atmosphere at 23 C. over a period of 0.5 hoursa solution of 7.3 g. (0.0455 mol) of 2,2,3,3-tetramethylcyclopropanecarboxylic acid chloride dissolved in 50 ml. of dry benzene. The mixturewas stirred at ambient temperature (25 C.) for 16 hours. Theprecipitated pyridine hydrochloride was filtered off and washed withbenzene. The combined benzene solutions were washed twice with 5-Nhydrochloric acid, once with water, twice with 2-N sodium hydroxidesolution, twice with 2-N hydrochloric acid, twice with saturated,aqueous sodium bicarbonate solution and twice with saturated, aqueoussodium chloride solution and then dried over anhydrous sodium sulphate.The sodium sulphate was filtered off, the filtrate was evaporated underreduced pressure, and the resulting syrup was distilled under highvacuum to yield 10.3 g. of4-phenoxy-2-butynyl-2,2,3,3-tetramethyl-cyclopropane carboxylate as acolorless liquid; boiling point (B.P.) l25-127 C./10- mm. Hg; n =l.5227.

Example 2 10.5 g. (0.534 mol) of 4-(4chloro-phenoxy)-2-butynl-ol wasdissolved in 70 ml. of dry benzene, and 8.5 ml. of dry pyridine wereadded to the solution. To this solution, there was then added dropwisewith stirring under a nitrogen atmosphere over a period of 5 hours at 20C., a solution of crude 2,2,3,3-tetramethyl-cyclopropane carboxylic acidchloride, obtained by chlorinating 7.58 g. (0.534 mol) of thecorresponding carboxylic acid, in 60 ml. of benzene. The mixture wasthen stirred at room temperature (25 C.) for 16 hours under a nitrogenatmosphere. The precipitated pyridine hydrochloride was filtered off andwashed with benzene. The combined benzene solutions were washed twicewith S-N hydrochloric acid, once with water, three times with 2-N sodiumhydroxide solution, once with 2-N hydrochloric acid, twice withsaturated, aqueous sodium bicarbonate solution and twice with saturated,aqueous sodium chloride solution and then dried over anhydrous sodiumsulphate. The sodium sulphate was filtered off and the filtrate wasevaporated to a syrup under reduced pressure. The crude product wasdistilled twice to yield 8.3 g. of 4-(4-chlorophenoxy)-2-butynyl-2,2,3,3-tetramethyl-cyclopropane car boxylate as acolorless liquid; B.P. C./-l0- mm. Hg; n =l.5329.

Example 3 8.8 g. of 4-(4-methyl-phenoxy)-2-butyn-l-ol was dissolved in'80 ml. of dry benzene, and 8 ml. of dry pyridine was added to thesolution. The resulting solution was then treated dropwise with stirringwith a solution of crude 2,2,3,3-tetramethyl-cyclopropane carboxylicacid chloride, obtained by chlorinating 7.1 g. of the corre spondingcarboxylic acid with thionyl chloride, in 20 ml. of benzene. The mixturewas stirred at 20 C. under a nitrogen atmosphere for 16 hours. Theprecipitated pyridine hydrochloride was filtered off and washed withbenzene. The combined benzene solutions were washed twice with 5-Nhydrochloric acid, once with saturated aqueous sodium chloride solution,twice with 2-N sodium hydroxide solution, once with 2-N hydrochloricacid, twice with saturated aqueous sodium bicarbonate solution and twicewith saturated aqueous sodium chloride solution then dried overanhydrous sodium sulphate. The sodium sulphate was filtered off, thefiltrate was evaporated and the residue was distilled under high vacuumto yield 11.65 g. of 4(4-methyl-phenoxy)-2-butynyl-2,2,3,3-tetramethylcyclopropane carboxylate; B.P. l20-126 C./l0 mm. Hg; n =1.52l3.

Example 4 By utilizing the procedure of Example 3,4-(3-methylphenoxy)-2-butyn-l-ol was reacted with crude 2,2,3,3-tetramethyl-cyclopropane carboxylic acid to yield 4-(3-methyl-phenoxy)-2-butynyl 2,2,3,3 tetramethyl-cyclopropane carboxylate;B.P. 145 C./10- mm. Hg; n =l.52l5.

Example 5 9.82 g. of 4-(3-chloro-phenoxy)-2-butyn-1-ol was dissolved in80 ml. of dry benzene, and 8 ml. of dry pyridine was added to thesolution. The resulting solution was then treated dropwise with stirringwith a solution of crude 2,2,3,3-tetramethyl-carboxylic acid chloride,obtained by chlorinating 7.1 g. of the corresponding carboxylic acidwith thionyl chloride in 20 ml. of benzene. The mixture was stirred at20 C. for 16 hours under a nitrogen atmosphere. The precipitatedpyridine hydro chloride was filtered off and Washed with benzene. Thecombined benzene solutions were washed twice with 5-N hydrochloric acid,once with water, twice with 2-N sodium hydroxide solution, once with 2-Nhydrochloric acid, twice with saturated aqueous sodium bicarbonatesolution and twice with saturated aqueous sodium chlo ride solution andthen dried over anhydrous sodium sulphate. The sodium sulphate wasfiltered ofi, the filtrate was evaporated and the residue was distilledunder high vacuum to yield 12.35 g. of 4(3-chloro-phenoxy)-2-butynyl-2,2,3,3-tetramethyl-cyclopropane carboxylate as an oil; B.P.l24132 C./- mm. Hg; n =l.5304.

Example 6 7.1 g. of 2,2,3,3-tetramethyl-cyclopropane carboxylic acid wasdissolved in 100 ml. of ethanol, and the solution was treated with 2-Nsodium hydroxide solution until the mixture had a pH of 7. The mixturewas evaporated under reduced pressure, and the residue was codistilledtwice with ethanol and three times with benzene. to constant weight.This yielded the sodium salt of 2,2,3,3-tetramethyl-cyclopropanecarboxylic acid.

The foregoing sodium salt was suspended in 400 ml. of dry diglyme andtreated with 9.0 g. of 1-chloro-4-pheuoxy butyne. The mixture was heatedat 140' C. with stirring for 6.5 days under a nitrogen atmosphere. Thediglyme was removed under reduced pressure, and the residue was treatedwith a mixture of water and diethyl ether and then extracted withdiethyl ether. The extracts were washed twice with 2-N sodium hydroxidesolution, once with saturated aqueous sodium bicarbonate solution, twicewith water and twice with saturated aqueous sodium chloride solution andthen dried over anhydrous sodium sulphate solution. Removal of thesodium sulphate by filtration, evaporation of the filtrate anddistillation of the residue in high vacuum yielded 7.05 g. of 4-phenoxy-2-butynyl-2,2,3,3-tetramethyl-eyclopropane earboxylate as an oil; B.P.140-150 C./ 10- mm. Hg; n ==1.5227.

Example 7 10.7 g. of 2,2,3,3-tetramethyl-cyclopropane carboxylic acid in25 ml. of petroleum ether was treated at room temperature (25 C.) with7.5 ml. of redistilled thionyl chloride and 2 drops ofdimethylformamide. After 1.5

room temperature, and the precipitated pyridine hydrochloride wasfiltered off and washed with benzene. The combined benzene solutionswere washed twice with 5-N hydrochloric acid, twice with 2-N sodiumhydroxide soludistillation of the residue under high vacuum yielded 10.0

g. of 4 chloro 2 butynyl-2,2,3,3 tetramethyl-cyclopropane carboxylate;B.P. l15-l20 C./0.7 mm. Hg: n =l.4900.

0.57 g. of sodium dissolved in 50 ml. of dry ethanol was treated with asolution of 2.35 g. of phenol in 20 ml. of dry ethanol, and the mixturewas left to stand for 2 hours. Then, the ethanol was removed byevaporation and the residue was codistilled three times with benzene toyield a white powder, the sodium salt of phenol.

The foregoing sodium salt was suspended in ml. of dry diglyme, and 5.71g. of 4-ehloro-2-butynyl-2,2,3,3- tetramethyl-cyclopropane carboxylatewas added thereto. The mixture was heated at C. for 48 hours under anitrogen atmosphere. The precipitated sodium chloride was then filteredoff. The solution was then evaporated under a water-pump vacuum andwater was added to the residue. The mixture was then extracted threetimes with diethyl ether, and the combined diethyl ether extracts werewashed once with 2-N sodium hydroxide solution and twice with saturatedaqueous sodium chloride ,solution and dried over anhydrous sodiumsulphate. Removal of the sodium sulphate by filtration, evaporation ofthe filtrate and distillation of the residue under high vacuum yielded3.95 g. of 4phenoxy-2-butynyl-2,2,3,3 tetramethyl-cyclopropanecarboxylate; B.P. 140445 C./ 10" mm. Hg; n =1.5227.

The following examples illustrate insecticidal com tions containing theesters of the invention.

Example 8 2.5 g. of 4-phenoxy-2-butynyl-2,2,3,3-tetramethyl-cyclopropanecarboxylate was dissolved in sufficient kerosene to give a final volumeof 100 ml. The resulting solution was suitable for use as a spray.

Example 9 5 g. of4-(4-chloro-phenoxy)-2-butynyl-2,2,3,3-tetramethyl-cyclopropanecarboxylate was well mixed with 5 g. of lignin sulphonate and 90 g. ofkaolin. The mixture .was thoroughly stirred in a mortar while 10 ml. ofwater was added, then the moist was further stirred and subsequentlygranulated in a granulator. After drying in air,

there were obtained granules containing 5% of active ingredient.

Example 10 20 g. of 4-phenoxy-2-butynyl-2,2,3,3-tetramethyl-cyclopropanecarboxylate, 10 g. of nonoxylon-lS (a non-ionic surfactant) and 70 g. ofxylene were thoroughly mixed wherein X is hydrogen, lower alkyl, orchlorine; and an inert carrier material.

2. The composition of claim 1 wherein said compound has the formula:

0-0-0 Hr-CEG-CHs-O- 10 3. The composition of claim 1 wherein saidcompound has the formula:

wherein X is hydrogen, lower alkyl, or chlorine.

References Cited UNITED STATES PATENTS 3,683,005 8/1972 Sota et a1.260-468 wherein X is hydrogen or lower alkyl substituted in the ortho orpara positions. VINCENT D. TURNER, Primary Examiner 4. The compositionof claim 1 wherein said compound comprises between about .5% by weightand 25% by weight of said composition. 25 260468 H

